DESCRIPTION: Fragility fractures that occur during everyday activities negatively impact the health and quality of life of many individuals who have a spinal cord injury (SCI). In order to decrease the incidence of fragility fractures in individuals with SCI, there is a need for the development of better rehabilitation strategies targeted at maintaining bone health. Therapeutic exercises that load the lower limbs have shown potential to modulate bone loss after SCI, but consistently beneficial results have not been demonstrated. Bone mechanobiology research indicates that the magnitude of skeletal force and the number of loading repetitions during exercising are key parameters affecting skeletal health. Yet, the mechanical stimulus imposed on the lower limbs during different types and intensities of rehabilitation exercises have not been well characterized or compared, making it difficult to assess their relative potential to modulate bone loss after SCI The key goals of the proposed research are to evaluate skeletal loading during four different SCI rehabilitation activities and to assess their relative potential to benefit skeletal health. Th results of this study have the potential to influence clinical practice by informing clinicians in he design of exercise protocols that will supply the lower limbs with sufficient mechanical stimulus to benefit skeletal health. The key goals will be addressed by collecting three-dimensional motion and force data while individuals with SCI perform four different rehabilitation exercises which load the lower limbs: 1) static weight bearing using a standing frame; 2) standing frame therapy with functional electrical stimulation (FES); 3) FES cycling; and 4) FES rowing. Two types of subject-specific musculoskeletal models (2D analytical models and 3D computational models) will be developed to estimate skeletal loading. Musculoskeletal models and simulations will be used to calculate the FES-activated muscle forces and the skeletal forces applied to the femur and tibia during each rehabilitation exercise. Exercises will be ranked according to the magnitude of skeletal force. The bone mechanical stimulus imposed on the lower limbs during each rehabilitation exercise will be estimated using the number of loading cycles during a typical exercise session and the average peak skeletal forces from each rehabilitation activity. The relative potential of each exercise to preserve bone density will be estimated based on the mechanical stimulus. The exercise dose that would be required for each rehabilitation exercise to produce an equivalent potential for bone health will also be calculated. These results will produce a valuable clinical resource for selecting rehabilitation exercises and activity doses which have the greatest potential to benefit skeletal health after SCI. This research study and training program will also serve to advance the applicant's career development through increased clinical exposure, advanced technical knowledge in musculoskeletal modeling, further development of clinical collaborations, and experience in the translation of research results into clinically meaningful applications. The data generated by this project will be used to design a future exercise intervention study to evaluate the effect of current and newly developed rehabilitation protocols on bone health after SCI. Additionally, the models and simulations developed for this study can be used to answer key questions about the setup and use of new or existing rehabilitation equipment or exercise techniques that could enhance the effectiveness of exercises. Results from predictive simulations that apply these models can inform physicians and therapists of modifications (e.g. cycle or rower seat position, adding weights or resistance, etc.) that could increase or decrease skeletal forces in a way that would be appropriate for each individual patient given their current skeletal status. This project represents an early step towar the ultimate goal of reducing the incidence of fragility fracture by developing better rehabilitatin protocols that can maintain bone health after SCI.